title: Clinical and radiographic features of the autosomal recessive form of brachyolmia caused by PAPSS2 mutations.
abstract: Brachyolmia is a heterogeneous skeletal dysplasia characterized by generalized platyspondyly without significant long-bone abnormalities. Based on the mode of inheritance and radiographic features, at least three types of brachyolmia have been postulated. We recently identified an autosomal recessive form of brachyolmia that is caused by loss-of-function mutations of PAPSS2, the gene encoding PAPS (3'-phosphoadenosine 5'-phosphosulfate) synthase 2. To understand brachyolmia caused by PAPSS2 mutations (PAPSS2-brachyolmia), we extended our PAPSS2 mutation analysis to 13 patients from 10 families and identified homozygous or compound heterozygous mutations in all. Nine different mutations were found: three splice donor-site mutations, three missense mutations, and three insertion or deletion mutations within coding regions. In vitro enzyme assays showed that the missense mutations were also loss-of-function mutations. Phenotypic characteristics of PAPSS2-brachyolmia include short-trunk short stature, normal intelligence and facies, spinal deformity, and broad proximal interphalangeal joints. Radiographic features include platyspondyly with rectangular vertebral bodies and irregular end plates, broad ilia, metaphyseal changes of the proximal femur, including short femoral neck and striation, and dysplasia of the short tubular bones. PAPSS2-brachyolmia includes phenotypes of the conventional clinical concept of brachyolmia, the Hobaek and Toledo types, and is associated with abnormal androgen metabolism.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Integrative Medical Science, RIKEN, Tokyo, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Pelin Özlem
authors.initials: PÖ
authors.lastname: Simsek-Kiper
authors.forename: Shuji
authors.initials: S
authors.lastname: Mizumoto
authors.forename: Touma
authors.initials: T
authors.lastname: Hoshino
authors.forename: Nursel
authors.initials: N
authors.lastname: Elcioglu
authors.forename: Eva
authors.initials: E
authors.lastname: Horemuzova
authors.forename: Stefan
authors.initials: S
authors.lastname: Geiberger
authors.forename: Gozde
authors.initials: G
authors.lastname: Yesil
authors.forename: Hülya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Gülen Eda
authors.initials: GE
authors.lastname: Utine
authors.forename: Koray
authors.initials: K
authors.lastname: Boduroglu
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004789:Enzyme Activation; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011859:Radiography; D013430:Sulfate Adenylyltransferase / Q000235:genetics* / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase
keywords: PAPSS2; androgen excess; brachyolmia; phenotype